title: Polymorphism -2604G>A variants in TLR4 promoter are associated with different gene expression level in peripheral blood of atherosclerotic patients.
abstract: Toll-like receptor-4 (TLR4) is a primary receptor of the innate immune reaction and compelling evidence demonstrates its involvement in the pathogenesis of atherosclerosis and stroke. TLR4 is constitutively expressed on monocytes and endothelial cells; it is highly expressed in atherosclerotic plaques and in peripheral blood of patients after ischemic stroke. Polymorphisms in the promoter region that alter the transcriptional regulation of this gene may represent genetic risk factors involved in the predisposition to atherosclerotic disease. In this study we investigated the effect on TLR4 gene expression of three polymorphisms in the upstream regulatory region at positions -1607T>C/rs10759932, -2026A>G/rs1927914 and -2604G>A/rs10759931 in peripheral blood of atherosclerotic patients. RNA from individuals homozygous for the -2604A allele showed a lower expression of the gene when compared to patients carrying the counterparts GG+GA. Electrophoretic mobility shift assays showed differences in the electrophoretic mobility of the DNA-nuclear protein complexes formed by the G>A variants, suggesting that the two alleles differ in their binding affinity to transcriptional factors.
authors.affiliation: Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ferronato
authors.affiliation: Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors.forename: Macarena
authors.initials: M
authors.lastname: Gomez-Lira
authors.affiliation: Section of Biological Chemistry, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Menegazzi
authors.affiliation: Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Diani
authors.affiliation: Section of Neurology, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Olivato
authors.affiliation: Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Sartori
authors.affiliation: Department of Vascular Surgery, University of Verona, Verona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Scuro
authors.affiliation: Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Malerba
authors.affiliation: Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors.forename: Pier Franco
authors.initials: PF
authors.lastname: Pignatti
authors.affiliation: Section of Biology and Genetics, Department of Life and Reproduction Sciences, University of Verona, Verona, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Romanelli
authors.affiliation: Section of Neurology, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Mazzucco
mesh_terms: D000368:Aged; D000483:Alleles; D050197:Atherosclerosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4